title: Ethanol- and acetaldehyde-induced cholinergic imbalance in the hippocampus of Aldh2-knockout mice does not affect nerve growth factor or brain-derived neurotrophic factor.
abstract: Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), play an important role in the maintenance of cholinergic-neuron function. The objective of this study was to investigate whether ethanol (EtOH)- and acetaldehyde (AcH)- induced cholinergic effects would cause neurotrophic alterations in the hippocampus of mice. We used Aldh2 knockout (Aldh2-KO) mice, a model of aldehyde dehydrogenase 2 (ALDH2)-deficiency in humans, to examine the effects of acute administration of EtOH and the role of AcH. Hippocampal slices were collected and the mRNA and protein levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), NGF and BDNF were analyzed 30 min after the i.p. administration of EtOH (0.5, 1.0, or 2.0 g/kg). We show that treatment with 2.0 g/kg of EtOH decreased ChAT mRNA and protein levels in Aldh2-KO mice but not in wild-type (WT) mice, which suggests a role for AcH in the mechanism of action of EtOH. The administration of 2.0 g/kg of EtOH increased AChE mRNA in both strains of mice. EtOH failed to change the levels of NGF or BDNF at any dose. Aldh2-KO mice exhibited a distinctly lower expression of ChAT and a higher expression of NGF both at mRNA and protein levels in the hippocampus compared with WT mice. Our observations suggest that administration of EtOH and elevated AcH can alter cholinergic markers in the hippocampus of mice, and this effect did not change the levels of NGF or BDNF.
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. Electronic address: jamaldr68@yahoo.com.
authors.forename: Mostofa
authors.initials: M
authors.lastname: Jamal
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ameno
authors.forename: Mostofa
authors.initials: M
authors.lastname: Ruby
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kinoshita
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000431:Ethanol; D020932:Nerve Growth Factor; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000079:Acetaldehyde
keywords: Acetaldehyde; Aldh2-KO mice; Cholinergic markers; Ethanol; Hippocampus; NGF and BDNF